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Volume 13
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Article

Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of Melanoma

by
Athanasios Seretis
1,2,
Lukas Amon
3,
Christoph H. Tripp
1,
Giuseppe Cappellano
4,5,
Florian Hornsteiner
1,
Sophie Dieckmann
1,
Janine Vierthaler
1,
Daniela Ortner-Tobider
1,
Markus Kanduth
1,
Rita Steindl
1,
Louis Boon
6,
Joke M. M. den Haan
7,
Christian H. K. Lehmann
3,8,9,10,11,
Diana Dudziak
3,12,13 and
Patrizia Stoitzner
1,*
1
Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, 6020 Innsbruck, Austria
2
Research Institute for Biomedical Aging Research, University of Innsbruck, 6020 Innsbruck, Austria
3
Laboratory of Dendritic Cell Biology, Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91052 Erlangen, Germany
4
Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases, Università del Piemonte Orientale, 28100 Novara, Italy
5
Center for Translational Research on Autoimmune and Allergic Disease-CAAD, Università del Piemonte Orientale, 28100 Novara, Italy
6
JJP Biologics, 00-728 Warsaw, Poland
7
Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Neatherlands
8
FAU I-MED, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91052 Erlangen, Germany
9
Deutsches Zentrum Immuntherapie (DZI), 91054 Erlangen, Germany
10
Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), 91054 Erlangen, Germany
11
Department for Paediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany
12
Comprehensive Cancer Center Central Germany Jena/Leipzig (CCCG), 07743 Jena, Germany
13
Institute of Immunology, Jena University Hospital, 07743 Jena, Germany
 
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*
Author to whom correspondence should be addressed.
Vaccines 2025, 13(4), 346; https://doi.org/10.3390/vaccines13040346
Submission received: 11 February 2025 / Revised: 14 March 2025 / Accepted: 20 March 2025 / Published: 25 March 2025
(This article belongs to the Special Issue Vaccines Targeting Dendritic Cells)
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Abstract

Background/Objectives: The revolution for the treatment of melanoma came with the approval of checkpoint blockade antibodies. However, a substantial proportion of patients show primary or secondary resistance to this type of immunotherapy, indicating the need for alternative therapeutic strategies. Dendritic cells (DCs) of the skin are prime targets for vaccination approaches due to their potential to prime naïve T cells and their accessibility. This study aimed to develop and evaluate novel vaccines targeting the C-type lectin receptor DEC-205 to deliver melanoma-associated antigenic peptides to skin DCs. Methods: We cloned MHC-I-restricted peptides from the glycoprotein (gp)10025–33 and Tyrosinase-related protein (trp)2180–188 into the DEC-205 antibody sequence with modified peptide cutting sites from the OVA257–264 SIINFEKL peptide. We tested their potential to induce CD8+ T cell responses in both in vitro and in vivo settings. Tumor growth inhibition was evaluated in the transplantable B16.OVA melanoma murine model using a multi-epitope DC-based vaccine combining both peptides. Results: The cross-presentation of both gp100 and trp2 peptides was confirmed in vivo when peptide sequences were flanked by the OVA257–264 peptide cutting sites. Moreover, the combination of both antigenic peptides into a multi-epitope DC vaccine was required to inhibit B16.OVA melanoma growth. Conclusions: Our findings suggest that a DC-targeted vaccination approach using multiple epitopes deriving from melanoma antigens could represent a promising strategy for melanoma therapy.
Keywords: dendritic cells; C-type lectin receptors; immunotherapy; melanoma antigens; DC-targeted therapy dendritic cells; C-type lectin receptors; immunotherapy; melanoma antigens; DC-targeted therapy

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MDPI and ACS Style

Seretis, A.; Amon, L.; Tripp, C.H.; Cappellano, G.; Hornsteiner, F.; Dieckmann, S.; Vierthaler, J.; Ortner-Tobider, D.; Kanduth, M.; Steindl, R.; et al. Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of Melanoma. Vaccines 2025, 13, 346. https://doi.org/10.3390/vaccines13040346

AMA Style

Seretis A, Amon L, Tripp CH, Cappellano G, Hornsteiner F, Dieckmann S, Vierthaler J, Ortner-Tobider D, Kanduth M, Steindl R, et al. Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of Melanoma. Vaccines. 2025; 13(4):346. https://doi.org/10.3390/vaccines13040346

Chicago/Turabian Style

Seretis, Athanasios, Lukas Amon, Christoph H. Tripp, Giuseppe Cappellano, Florian Hornsteiner, Sophie Dieckmann, Janine Vierthaler, Daniela Ortner-Tobider, Markus Kanduth, Rita Steindl, and et al. 2025. "Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of Melanoma" Vaccines 13, no. 4: 346. https://doi.org/10.3390/vaccines13040346

APA Style

Seretis, A., Amon, L., Tripp, C. H., Cappellano, G., Hornsteiner, F., Dieckmann, S., Vierthaler, J., Ortner-Tobider, D., Kanduth, M., Steindl, R., Boon, L., den Haan, J. M. M., Lehmann, C. H. K., Dudziak, D., & Stoitzner, P. (2025). Multi-Epitope DC Vaccines with Melanoma Antigens for Immunotherapy of Melanoma. Vaccines, 13(4), 346. https://doi.org/10.3390/vaccines13040346

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